Clark Robert E, Broadbent Nicola J, Squire Larry R
Veterans Affairs Medical Center, San Diego, California, USA.
Hippocampus. 2005;15(3):340-6. doi: 10.1002/hipo.20076.
Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks, and it has figured prominently in theoretical treatments of memory and hippocampal function. A striking exception to the finding of temporally graded retrograde amnesia comes from studies with rodents using spatial tasks like the water maze. In these studies, recent and remote memory were similarly impaired following hippocampal lesions. In contrast to work with rodents, studies of patients with medial temporal lobe lesions, including complete hippocampal lesions, indicate that remote spatial memory can be intact. One difference between studies in humans and studies in rodents is that spatial memory in animal studies is acquired during a limited period of time when the animals are adults. In contrast, the spatial memory studied in humans was acquired beginning at an early age and learning continued for a considerable period of time. We initiated training in a standard water maze immediately after rats had been weaned at 21 days of age and continued training until the rats were young adults (90 days old). Large hippocampal lesions were made 100 days after the completion of training. After recovery from surgery, control rats exhibited good retention on the first retention probe trial, but rats with hippocampal lesions performed at chance. Thus, even after extended training beginning early in life, and with a prolonged training-surgery interval, hippocampal lesions impair performance in the water maze task. Possible reasons for these findings are discussed in the context of the specific performance requirements of the water maze task.
海马体受损通常会导致时间梯度性逆行性遗忘，即近期获得的记忆比远期获得的记忆受损更严重。这一现象已在多种物种和任务中反复得到证实，并且在记忆和海马体功能的理论探讨中占据重要地位。时间梯度性逆行性遗忘这一发现的一个显著例外来自对啮齿动物进行的使用水迷宫等空间任务的研究。在这些研究中，海马体损伤后近期记忆和远期记忆同样受损。与对啮齿动物的研究不同，对内侧颞叶损伤患者（包括完全海马体损伤患者）的研究表明，远期空间记忆可能完好无损。人类研究和啮齿动物研究之间的一个差异在于，动物研究中的空间记忆是在动物成年后的有限时间段内获得的。相比之下，人类研究中的空间记忆是从幼年开始获得的，并且学习持续了相当长的一段时间。我们在大鼠21日龄断奶后立即开始进行标准水迷宫训练，并持续训练至大鼠成年（90日龄）。在训练完成100天后进行大面积海马体损伤。手术后恢复后，对照大鼠在首次记忆探测试验中表现出良好的记忆保持能力，但海马体损伤的大鼠表现随机。因此，即使从生命早期开始进行长时间训练，并且训练与手术间隔时间延长，海马体损伤仍会损害水迷宫任务中的表现。本文在水迷宫任务的特定表现要求背景下讨论了这些发现的可能原因。
